Ethics in Psychiatric Research.

INTRODUCTION AND SCOPE

Research is essential for the progress of science. Research builds upon the already available knowledge base and expands the horizons by enhancing the scientific evidence incrementally. Similar to other branches of medicine, psychiatry also requires research to be conducted ethically, safeguarding the rights and privileges of the research participants.[1] Ethics deals with the appropriate manner of conduct of professionals and provides the guiding principles of how decisions should be taken. Ethics is broad in scope and applies to many facets of research. Consideration of ethics and ethical issues starts from the time of conceptualization of research and continues to operate even after the completion of the research. Medical ethics has been built upon the principles of autonomy, beneficence, nonmaleficence, and justice.[2] However, there are many other considerations and nuances that pertain to ethics and ethical decision-making [Table 1]. The conduct of research should aim to adhere to ethical principles, though not all principles would be applicable equally in all situations. For example, a study on sexual perversions would probably need to have a greater emphasis on autonomy and confidentiality than a study that looks at the sexual side effects of medications. Researchers should be mindful of the various ethical issues while planning research.

Table 1

Terms relevant to ethics in psychiatry research

• Autonomy: Participant should have the right to choose whether they want to partake in research

• Beneficence: The primary aim of researchers is the benefit of the participants

• Nonmaleficence: Applies the principle of “do no harm,” and encourages researchers to reduce the potential harm to the participants

• Justice: Obligation to act fairly and using the principle of equality for competing claims

• Confidentiality: Researcher should maintain confidentiality and anonymity of the participants

• Deontological ethics: Stance that some actions and inherently right and some actions are inherently wrong

• Ethical conflict: Choice between two courses of action, one ethically correct and one ethically wrong

• Ethical dilemma: Choice between two courses of action, both ethically defensible

• Slippery slope argument: Stance that small unethical actions if accepted may lead to more unethical actions incrementally

• Utilitarian ethics: Stance that actions are correct if the ends achieved are good

Another issue is that though ethical principles are largely consistent, the conceptualization of what is ethical and what is not, is likely to vary with time in history, geographical location and perceptions of the community.[3] For example, it might have been considered ethical to conduct research on minors with just parental approval in the past, but current-day ethical practices in research necessitate that assent from the minor should also be obtained in addition to parental or guardian’s consent. The reverse is also essential in the current-day context. Getting assent from minor may not be sufficient, and additional consent from the parents/guardian is also required. Thus, current-day ethical notions should be followed in the planning and conduct of research. The best practices have generally been adopted the world over, though there may be variations in the manner in which some aspects are considered relevant and applicable. One needs to be aware of the current ethical standards, and the present guidelines attempt to provide an insight into the current ethical yardsticks with respect to psychiatry research. This guideline aims to discuss and describe the ethics of psychiatry research. The ethical principles and concepts in relevance to psychiatry research are discussed and described. One does need to consider that there might be dilemmas (i.e., two or more correct courses of action) and ethical conflicts (a contest between ethically correct and incorrect). While much leeway is granted for dealing with ethical dilemmas, ethical conflicts should be completely avoided. These guidelines should be read with the Declaration of Helsinki and ethical guidelines issued by the national organizations, such as the Indian Council of Medical Research (ICMR). However, if still some of the issues remain unanswered, then the researchers should seek guidance from the Institutional Ethics Committees or other bodies recognized by the ICMR for supervising research.

DECLARATION OF HELSINKI

The World Medical Association (WMA) has adopted the Declaration of Helsinki in 1964,[4] which is a statement of ethical principles for medical research involving human subjects. The declaration primarily addresses the physicians, though the WMA envisions adopting these principles by others involved in medical research involving human subjects. Since psychiatry is a discipline of medicine, the Declaration of Helsinki applies to psychiatry as well. The original declaration has been further amended on several occasions, the last one being in the 64th General Assembly of WMA, Fortaleza, Brazil, in October 2013.[5]

The various provisions of the Declaration of Helsinki cover different aspects of ethics in the medical field and provide guidance about planning, conducting, and disseminating research. The Declaration has become a standard for compliance to ethical issues and are often referred to before publication of research findings in most reputable journals. The principles emphasize that physicians should work in the best interests of their patients and also remarks that continued research is important. The principles underscore the need to promote and ensure respect for all human subjects and protecting the life, health, dignity, integrity, right to self-determination, privacy, and confidentiality of personal information of research subjects.

The principles suggest that ethical, legal, and regulatory norms should be followed while conducting any kind of research [Table 2]. Minimization of the risk of harm to the participants should be attempted, and the research endeavors should be carried out by those who have adequate training and competence. Adequate compensation for those harmed by research needs to be ensured, and caution has been expressed for the referral and recruitment of patients by physicians who combine research and medical care. Risks, benefits, and burden of research should be carefully weighed, with attempts to minimize risk, conduct of research when the importance of objectives outweighs risks, and involvement of physicians in research if the risks have been suitably evaluated and are deemed to be satisfactorily manageable.

Table 2

Some of the basic general principles of declaration of helsinki

• Physicians should work in the best interests of their patients

• It is the physician’s responsibility to promote and safeguard the rights, health, well-being, dignity, integrity and privacy of the patients participating in medical research

• Medical research on humans should be conducted by individuals having appropriate competence

• Clinicians involved in research should follow the ethical codes and regulatory norms, set out at the national and international level

• Risks to participants should be estimated and minimization of risk should be implemented

• Specific protections should be in place for vulnerable groups

• Approval from ethics committees prior to initiation and subsequent monitoring of the study is required

• Privacy and confidentiality of the participants should be maintained

• Participants should be recruited after obtaining informed consent from the participant or legally acceptable representative

• New interventions should be tested against best-proven treatment(s)

• Every research study on humans should be available in a publicly available database, and the scientific community is obligated to disseminate the research work

• Efforts should be made to make interventions available posttrial if the intervention is found to be beneficial

In addition, the Declaration of Helsinki specifically takes into consideration the protection of vulnerable populations. The health needs and priorities of the vulnerable groups should be considered while planning a research study among them so that they are final beneficiaries. The Declaration also mandates protocolization of the research proposal, which should have mention of the ethical considerations along with funding, institutional affiliations, potential conflicts of interest, incentives for subjects and information about treatment and/or compensation of those who are harmed as a consequence of research. A transparent and independent ethics committee should have approved the protocol before the conduct of the study. The Declaration lays emphasis on the privacy and confidentiality of the personal information of the participants. Emphasis has been laid on obtaining informed consent from the participant or legally authorized representative, ensuring that there was no duress. The Declaration allows proceeding with the research. Even if the participant is incapable of giving informed consent, no legally authorized representative is available. If the research cannot be delayed, provided such a situation has been stated in the research protocol and a research ethics committee has approved the study. The Declaration also provides for all medical research subjects being given the option of being informed about the outcomes and results of the study.

The Declaration generally dissuades against the use of placebo except when no proven intervention exists, or where no intervention is acceptable. Furthermore, the continuation of intervention after the completion of the research should be given consideration. Finally, the Declaration suggests that studies should be registered in repositories before recruitment of the first participant and that the research findings should be disseminated. Unproven intervention should only be used in research for situations where the proven intervention are not available or are ineffective. In such circumstances, the information should be available publicly.

Whether there is a need for research is the first consideration for the conduct of the research. Inane or duplicitous research creates confusion, wastes human and material resources, and may lead to societal discomfort with the research endeavors. Thus, the first consideration for any research after the decision of the topic is whether the research is needed [Table 3].

Table 3

Selection of research topics in the field of psychiatry

• Look for novel topic for research

• Topics should be selected to keep in mind the applicability of the findings in the routine clinical practice or further the knowledge about understanding the disorder in questions

• Consider feasibility into account while selecting the topic

• While selecting the topic for research, avoid duplication/replication of the previous studies

• On the other hand, findings of some of the studies, which have been done in western countries or different socio-cultural background, may not be directly applicable to local setting and hence, replication may be considered

• While considering replication studies, it is important to introduce the specific issues relevant to the Indian setting, much be introduced in the methodology, and make the findings more relevant

• Thesis guides or supervisors should suitably mentor trainee professionals in research pursuits about selection of relevant topics

• Ideally, every research study should be published

There can be several ways of considering whether research is required in a specific field, sub-branch, or topic in psychiatry. The need can be guided by what is necessary to advance the field. For example, Genome-Wide Association Studies may be needed to understand what Single Nucleotide Polymorphisms are related to a disorder, though it may be resource-intensive and many need multi-centric collaboration. The need may also be guided by what is relevant to clinical practice and what describes the availability, impression, efficiency, variety, and execution of care and care processes. For example, what are the issues experienced during care provided for dissociative disorders? What is relevant is generally dictated by the research trends or interests of the time. Repeating an experiment or research findings is useful to a certain extent to provide external validity for the research and address some of the issues that have not been covered by the existing study. But such replication of studies beyond a certain point makes research endeavors irrelevant.

In the current scenario of expansion of research endeavors, it is furthermore necessary to adhere to ethical frameworks. Ethics dictate professional domains of work. It is important to have regulation of the practice so that the profession thrives, is taken seriously, can weed out gross incompetence and misdemeanors, and can cater to social needs responsively. Research in the professional framework also operates in the ethical boundaries of the profession. This would help to keep the profession’s standing intact in society’s opinion, which is likely to enhance confidence, application, and acceptability of the professional services. For example, enhancing psychedelic research in the field of psychiatry is liable to send mixed messages to the community in the current circumstances and probably requires closer scrutiny and regulation.

The ethical implication of consideration of the need for research endeavor is the potential harms to the research participants and blocking of resources for research pursuits that can be utilized elsewhere. All studies, even survey based, have some risk to the participants, even though it may be minimal. Some kinds of studies, for example, drug trials, may have a higher risk of harm to the participants. Thus, the considerations for participants would be important while designing and planning research in psychiatry. Furthermore, research endeavors take up some resources, in the form of time and energy of researchers and participants, and material resources from healthcare or other services. While the allocation of such resources is important to produce effective research, duplication/replication of research after certain extent must be avoided which have negligible incremental benefit for science. Yet, considered leeway is important to enable diverse opinions and points of view to be expressed.

STUDY DESIGNING: LANGUAGE AND PERMISSIONS FOR THE USE OF INSTRUMENTS

One of the important issues while planning research in psychiatry pertains to the selection of instruments [Table 4]. The two most important issues which are of paramount importance are the language in which the instrument is available and whether the use of the instrument requires any prior permission. At times, researchers end up using questionnaires/scales developed in other countries without considering the socio-cultural issues and linguistic issues, which would be important when conducting the research. On-the-spot translation of a scale developed in another language and cultural background should be avoided.

Table 4

Ethical issues, related to the selection of instruments for the study

• Use validated instruments to carryout the research

• Seek permission from the copyright holder of the instruments

• Check the instruments, whether these require adaptation and validation in Indian setting

• If adaptation and validation is required, do so, by following the standard recommended methodology

• If you are designing any instrument, validate the same, prior to use in the main study

• Avoid on-the-spot translation for various scale items at the time of administration of the scale

Many of the instruments are available free of cost in the public domain. Some of the instruments are available in the public domain, but use requires seeking permission. Some of the instruments are only available with the copyright holders and the vendors. It is generally suggested that if a researcher is planning to use certain instruments, it is advisable to seek permission from the person holding the copyright for the instruments. Many a times, people end up using various instruments in research without obtaining permission and face problems at the time of publication. Hence, it is suggested that these issues must be addressed before starting of the research. Further, it is also well-known that many of the instruments, which have been designed in different parts of the world, are not directly applicable to the Indian setting and may require adaptation and translation. It is better to carry out these exercises before planning the bigger study, so the instrument’s psychometric properties, which are planned to be used, are available beforehand. If these steps are not followed beforehand, it may lead to difficulty at the time of publication and, ultimately, nonpublication of the research. Nonpublication of research basically means a lack of value attached to the time devoted by the researchers and participants in the study, which can be considered as unethical. It is important to remember than many of the authors, who have the copyright of various scales, often allow permission for the use of various instruments, free of cost, for nonfunded studies. Hence, the authors should conduct a proper search to address these issues at the time of planning the study. Another issue that often arises at the time of publication of research is the use of self-designed instruments. While doing so, it is always better to validate the instrument by using the appropriate methodology.

VETTING FROM ETHICS COMMITTEES

Any kind of research should preferably be conducted after approval from a competent ethics committee. Ethics committees are able to reduce the biases of individuals and provide diverse opinions on the process of research matter. Ethics committees in the present-day context are constituted in institutions which conduct research. Apart from this, there are independent ethics review boards as well, which cater to researchers who are not affiliated with institutions. The role of the ethics committee is paramount before the conduct of research. The proposal of research is evaluated by the committee, which attempts to ensure that the rights of the patients are respected, and the study is planned to be conducted in an ethical manner. Generally, the ethics committees do not delve into the merits of the methods of the research. They are more focused on whether the researchers commit to ethical benchmarks to be followed during the research. Generally, institutional ethics committees are composed of individuals from the institute and some external members and observers, some of whom may be nonexperts, or experts from legal background and lay members of the community. External members are necessary to obviate the blind spots and bias that clinicians, academicians, and researchers bring in their decision-making processes. The Indian Council for Medical Research (ICMR) has provided guidelines for setting up ethics committees.[6] A researcher who is working alone or whose institution does not have an ethics committee can approach a nearby ethics committee in another institution or an independent ethics committee. For drug trials, the Central Drugs Standard Control Organisation mandates that the ethics committee should be registered with it.[7]

One question that comes up is what kinds of research should have ethics committee approval. It is desirable to have approval for any kind of research endeavor. Some research pursuits which are presented in the form of case reports and case studies may not provide an opportunity to plan and hence may not offer a prospect of ethics approval. However, for publication purposes, it is important to anonymize the details of the patient, and informed consent of the patient should be obtained before publication of the case details. Ethical consideration of confidentiality should be paid attention to while publishing pictures/images which have the potential of disclosure of the patient’s identity.

However, other studies such as retrospective studies, observational studies, and interventional studies should have a-priori ethics approval before conduct of the study. Ethics approval and close oversight is very much essential for studies dealing with electroconvulsive therapy or psychosurgery and in active comparator psychotherapy studies where the group allocation is not explicitly disclosed to the participants. In certain circumstances like disasters and emergency situations, many ethics committees offer a provision for expedited review or provisional approval pending usual procedural scrutiny.

A point of contention that may sometimes emerge is what to do when the ethics committee objects to some or many of the research objectives, methods, or processes. This might be disheartening to the prospective researcher, but it is important to understand the ethics committee’s concerns and reasoning. Generally, it might be possible to get the reasons of noted objections of the ethics committee. One may not totally agree and be satisfied with the reasoning provided, if at all, but the reasoning may reflect collective inference of the situation and research proposal. Sometimes, a foregoing brilliant research proposal to safeguard the research participants’ perceived interest may be important. An objection or refusal should be taken up with a sporting spirit and pondered upon after a period of “cooling off” of emotions.

There is some consensus about the kind of studies, which may not require ethical clearance. Secondary analysis, such as systematic review, metanalysis, and meta-regression, may not require ethical clearance, but may be registered with the trial registry. Similarly, for the publication of case report/small case series, ethical clearance is not required, but many journals require the consent of the patient(s). Some of the studies may not require direct use of data but may involve the use of the system data. For example, someone wants to evaluate other clinicians’ opinions about functioning of the particular services without collecting any specific patient-related data. This can qualify for an application of waiver from the ethics committee. At other times, the researcher wants to use some of the data available in the public domain to study a particular question. For such a scenario, there are no clear-cut guidelines. However, the basic principle should be that, whenever in doubt, it is always better to seek ethical clearance for the study.

NEED FOR REGISTRATION OF STUDY IN A TRIAL REGISTRY

For interventional studies of any type, be it psychotherapeutic, pharmacological or stimulation based, it is desirable to have the study registered in a trial registry. The ethical considerations for such trials pertain to making information available to the general public about a trial with a particular methodology being conducted. This helps in preventing wastage of resources through duplicate efforts and thus serves the principles of justice. This also helps in participants feeling accounted for, and the results from their findings more accessible to the community in general. A research on participants does expose them to some risks, even though it may be minimal, and takes away time and resources. If the results are inaccessible to others, then the potential benefits of the research (even whose findings were negative) are not available to others. Many a times, the results are not published, with the reasons being journal preferences and thresholds and attrition of interest of the researcher. But if a trial is registered, then the researchers can be approached by interested parties about the findings. Hence, it bridges the gap between research conduct and access to the results. Thus, trial registration in a publicly accessible database is an ethically correct stance. The trial registry in India is the Central Trial Registry of India (CTRI). The researchers can apply for registration of the trials/studies after obtaining ethical clearance for the study. For observational studies, the CTRI does not clarify whether registration is required and leaves the decision to register for “purely observational study” on the researcher, stating that “The CTRI is a facilitator body that provides a platform for registering clinical studies as mandated by the drug licensing authority, ethics committees and journal editors. Further, the WHO advises “When in doubt, register.” For purely observational studies CTRI registration is not mandatory.

PROFESSIONAL COMPETENCE

It is, in general, suggested that research need to be taken up by persons who are qualified and have time for the same. Further, the researchers are expected to work with total integrity and impartiality and are expected to be aware of all the ethical considerations which may be required to conduct the research or experiment.[1]

ETHICAL ISSUES PERTINENT TO THE ENROLMENT OF SUBJECTS INTO THE STUDY

Once the research has been duly approved by the ethics committee and registered in the required trial registry, the next important step involves the enrolment of the participants. Some of the important ethical issues that are to be considered at the time of enrolment include autonomy, informed consent, and confidentiality.

AUTONOMY

While enrolling for a study, participants should be given a choice of whether to participate and not to participate at all in the research or leave in between after initial consent for participation on their free will without loss of benefits that they are otherwise entitled to. Potential participants may feel obligated or coerced to participate in research if their treating clinicians nudge them towards participation. This may be a consequence of perceived power differential, transference experienced by the patient, or a feeling of obligation to the care provider. It is important to explicitly clarify to the potential participants that the participation would be voluntary. This may be a point of contention from the researcher’s perspective, especially if a large number of patients refuse participation in treatment, leading to abysmal recruitment rates, which in turn may result in a lack of meaningful inferences drawn from the research endeavor. Nonetheless, the participants’ autonomy should be respected, and participants should be clearly explained that decision to participate is based on their own will.

Things become a little murky when the potential participant is unable to provide consent due to lack of capacity or being a minor. An individual is deemed to lack the capacity to consent if he or she is unable to understand and appreciate the consequences of choices of actions available, to decide on a course of action, and communicate it clearly.[8] Therein, consent can be obtained from a guardian or a legally acceptable representative (LAR). Still, in such a situation, concurrence from the participant is desirable. A mere presence of a psychiatric disorder like schizophrenia or bipolar disorder, where the judgment may be grossly impaired, may not affect the capacity. Thus, capacity should be the focus when assessing the suitability of the person to give informed consent. For minors, consent should be obtained from the guardians or parents and assent should be obtained from the minor participants. If the guardian agrees and the minor disagrees to participate, in such situation, it is better to avoid including such a participant in the research.

A construct that seemingly intersects with consent to participation in research pertains to inducement. Inducement is considered as any reward for participation in research, which is more than the compensation for the time and efforts invested in research. Inducement may be monetary, voucher or special treatment privileges that are not given to the nonparticipants. Inducements nowadays are considered to affect autonomy in decision-making, and hence are seriously considered by the ethics committees. Excessive potential rewards of participation may make the participant overlook the harms anticipated due to the participation in the study. Hence, it is important for researchers to refrain from using inducements.

INFORMED CONSENT

The explicit consequence of ensuring autonomy is taking informed consent from the participants (or their LARs). Informed consent has two parts: Information being provided to the prospective participant about the research, and consent being taken for voluntary participation. The first part is giving information to the participant. Ideally, all research proposals should have participant information sheets which provide information about the study in layman language. The information provided generally include who are the researchers (and their contact details), what are the aims of the research, how the research would be conducted, what steps would be taken to ensure confidentiality, what are the harms that are anticipated and who would reimburse for such harms, whether the participant is expected for pay for the research investigations or whether he/she likely to get any material benefits from participation in the research, and what are the loss of benefits that the likely to be accrued if the potential participant declines to participate or leaves during the research. The information should be provided in the language the potential participant is able to read and write easily, and should avoid jargon [Table 5]. The participants should be handed over the information before obtaining written informed consent. They should be allowed sufficient time to go through the whole information sheet and be allowed to keep a copy of the information sheet.

Table 5

Particulars to be mentioned in the patient information sheet document

• Name of the research project with names of the investigators (with contact details)

• Purpose of the study

• Aims of the proposed study

• Procedure of the study and study duration

• Number of times the assessment will be conducted (cross-sectional/multiple)

• Maintenance of strict confidentiality

• Details of participant’s contribution (such as psychological tests, laboratory investigations, filling questionnaires, etc.)

• Perceived benefits/material benefit the participant will receive

• Any anticipated harm/risks (foreseeable and unforeseeable)/discomfort/adverse effects to the participant from the study and reimbursement process/insurance benefits in case of such harms

• Details of payment for the research investigations if the participant has to pay or is exempted

• Explanation that the participants can leave the study midway and if so, expected loss/benefits to the participant

• Any incentives to be provided for participation

• Provide information to the patient, if any new information emerges on the topic

• Prospective research benefits to self or to the community

• Statement about possible current and future uses of biological material and data collected for research (whether it will be used for secondary purpose or shared with others)

• Whether the participant is able to follow the information adequately and in case of any questions/suggestions where/whom to contact for any questions

• The patient information sheet needs to be provided in the patient’s mother tongue or local language

• Funding agency

• Use of the data generated: Publication, presentation

• Information about the ethics committee and contact details

• Signatures of the investigator and participant along with date and place of signing

• The informed consent form need to be prepared separately in English and vernacular languages

• Every participant and the researcher must sign two copies of the informed consent form; one of this must be given to the participants

To reduce the problems associated with recall biases about whether consent has been taken or not, it is better to have a ‘written informed consent’ which bears the signatures of the consent provider that he/she has understood the risks and harms associated with the research and is voluntarily participating in the research endeavor. Such written informed consent is often endorsed by witnesses to make it a formal witnessed document. In some situations, the consent informed consent process is also audio and/or video recorded to provide even further assurance that due processes have been followed. More recently, the Supreme Court of India had mandated for the audio-visual recording of informed consent to be done mandatory in cases of research on vulnerable populations, clinical drug trials and with new chemical entities (Supreme Court on India dated July 31, 2015).[910] In some cases (for example, telephonic interviews), verbal consent is deemed adequate. For online questionnaires, consent is implied if the individual ticks on the checkbox meant for eliciting the consent.

The basics of the informed consent form are given in Table 6.

Table 6

Basic things which needs to be mentioned in an informed consent document

• Written informed consent form

• Should be in patient’s/participant’s local language or can be easily read/understandable

• Should mention if the information provided to the participant has been clearly conveyed/understood by the participant

• That the participant is taking part in the study/research at his own will i.e., under no coercion

• Has understood the risks/benefits associated with the research

• Signature of the participant, investigator and a witness with date, time and venue

• Provide consent/permission for audio-visual recording (drug trials)

• Can withdrew consent or declare for nonparticipation at any time point of the study without getting affected by any means (no change in treatment)

• Verbal consent

• All the above mentioned points need to be discussed with the participant and the participant agrees for his participation

• The statement of agreement for participation can be audio recorded

• Electronic/web-based/online survey related consent

• The participants may be asked to proceed ahead after going through a brief introductory message explaining the purpose of the study, time required for the survey and details regarding confidentiality and anonymity

• If the participant agrees to participate, merely clicking the link provided or proceeding ahead with “Yes” option in the introductory message signifies that the participant agreement for participation; option of “No” should also be available to refuse to participate in the study

In certain special situations, the research can be conducted without consent, i. e., informed consent can be waived off. These include (1) if it is almost impracticable to obtain consent (for e. g., homeless/institutionalized patients with severe cognitive decline) (2) the research does not compromise with the principle of self-determination, i. e., the gravity of rights infringement is minor/negligible and this is outweighed by the expected value of the research to the society and (3) the research is of significant clinical relevance.[1112] However, such decision needs to be approved before the start of the study by the Institutional Ethics Committee (IEC) or Institutional Review Board (IRB). The guidelines of the ICMR do not provide for an exemption or expedited review. However, ICMR guidelines permit waiver of informed consent, provided that the study is of minimal risk or is conducted in an emergency.

CONSENT AND RESEARCH IN SPECIAL POPULATIONS

Special populations include children, pregnant women, those with low mental capacity (intellectually disabled/persons with dementia), and institutionalized individuals (prisoners, homeless/destitute, etc.). Psychiatric research in these special groups needs more strict protocols to be followed, emphasizing the nature of informed consent and its implications.

Children and adolescents

Legally a child or an adolescent below the age of 18 years cannot provide informed consent for participation in any study. Therefore, the researcher has to take informed consent from the parent or legal guardian after explaining in detail about the purpose of the study and answering to all their queries related to risks and benefits to the child/adolescent. The parent/legal guardian can sign on behalf of the child/adolescent on the written informed consent form. If a child/adolescent is capable of understanding some part of the study, then the child’s agreement for the same needs to be taken which is otherwise known as assent. Typically, a child of at least 7 years of age can be asked to provide assent for his/her participation. In detail, the researcher should mention the exact procedure of taking assent or informed consent from parents to the IRB at the time of submission of the project. The IRB’s responsibility is to thoroughly examine the cost-risk estimate of enrolment of this group of the population before approval of the study.[1314]

Pregnant women

The Office of Human Research Protection of United States, as well as the national health authorities of every country (ICMR for India),[6] have issued guidelines and policy statement on ethical issues to be considered in research involving Human subjects and these clearly state that it is the Ethics Committee’s responsibility to review any research on pregnant women and evaluate whether it is justifiable enough to be carried out or not. It has also been stated that the Ethics Committee can consult any representative of the vulnerable population to get their view point on the study subject while reviewing the protocol, so as to prevent even minor exploitation.[15] Additional information to be provided while informing about study to pregnant females involves explaining in detail any possible risks that may come to the fetus by participating in the experiment. This includes information of prior research involving animal models and nonpregnant women. To perform experiments on a mother, a researcher must obtain legally effective informed consent, where both parents are required to consent when the research involves the fetus.

Adults with impairments

Decisionally impaired individuals are adults with diminished ability to make sound judgments due to flaws in their reasoning from psychiatric, organic, developmental or other disorders of a cognitive or emotional nature. Most often, these people have a caretaker, whether family or professional, who is involved in their care. These caretakers can have legal guardianship, meaning they can decide for the participant to partake in the study. This should be informed to the IRB and accordingly, the informed consent form needs to be designed.[15] The issues related to the nominated representative as per the Mental Health Care Act, 2017 (MHCA, 2017)[16] also need to be given consideration in this regard.

Proxy consent

Proxy consent is understood as informed consent that is provided by a surrogate decision-maker on behalf of a patient. A proportion of patients with mental illness, especially those with severe mental illnesses, dementia and delirium lack decisional capacity as a result of impairment in mental faculties; moreover, competence in decision making is not a static construct and may vary as a function of illness status and severity. In instances where the patients lack competence, a commonly accepted practice is to obtain informed consent from a legally accepted representative (LAR) who acts as surrogate decision-makers on behalf of the patients. In India, the LAR is usually the spouse or guardian of the patient.

Accordingly, in such situations, proxy consent by LAR is ethically proper and appropriate provided that the process of obtaining the consent from LAR meets the requirements of substituted judgment and the best interest. The principle of “substituted judgment” means that the LAR can exercise the choices that the patient would have exercised if he/she were not impaired and could have exercised their choice. In other words, the LAR can think like the patient while making decisions about the patient’s preferences. The principle of “best interests” basically means that the LAR is able to exercise his/her choice in the best possible manner that he/she believes would further the interests and well-being of the patient under their care. According to the MCHA, 2017, the nominated representative can provide proxy consent in case the patient lacks capacity. Proxy consent is particularly applicable to research involving critical care patients in whom certain life-saving interventions are planned and there are several viewpoints on its ethical analysis.[17] The validity of proxy/surrogate consent in psychiatry clinical studies has been a debatable topic. In general, consent can be obtained from the LAR when the subject is incompetent, and a legal guardian is considered LAR. If a LAR does not exist, many associations (e.g. American Psychiatric Association) have recommended involving the IRB’s representative or a patient advocate to authorize for the subject’s participation or ask suggestions from the second physician/clinician’s opinion regarding subject’s participation.[18] It has been suggested by the National Institute of Health that for studies with greater direct benefits and lesser estimated risks, the LAR’s consent may be acceptable unless there is strong/adequate evidence showing opposed preferences of the subject.[19] However, there are several issues related to ethics of involving decisionally incapable adults in research more so in geriatric and neuro-psychiatric researches which needs proper guidelines.[20]

WAIVER OF CONSENT

In some situations, the researchers can seek for waiver of the consent from the Ethics committee [Table 7]. However, proper justification for the same must be provided to the ethics committee. Further, it is to be understood that waiver of the informed consent actually means waiver from documentation of the informed consent. However, the research team has to provide information (i.e., things as part of the information sheet), but is not required to have the signature of the participants on the informed consent form. However, it is important to note that researchers should not apply for waivers in research involving the collection of biological specimens.

Table 7

Types of studies that do not require ethical clearance or for which waiver from the ethics committee can be applied for

1. The ethics committees may consider waiver of consent for retrospective studies with anonymized data

2. Waiver of informed consent (with due approval from an ethics committee) can be considered for research that involves minimal risk for subjects. The research cannot be carried out practicably without the waiver, and the waiver does not affect the rights of the patient

3. For deception research, waiver is often coupled with provision of debriefing after the study

4. Waiver of documented informed consent can be considered for studies conducted through online/telephone surveys; or for studies where breach of confidentiality can lead to harm (for example, studies on individuals who have faced domestic violence)

5. For research involving emergency care where there is more than the minimal risk to the prospective study participants, provided that there is a direct benefit to the participants and other conditions for such a research are met

CONFIDENTIALITY

Psychiatric and substance use disorders are often associated with stigma.[212223] Thus, confidentiality issues have to be taken seriously while conducting research in psychiatry. It is unlikely that the participant appreciate being identified by others in their social discourse due to just partaking in the research pursuit. Hence, research often aims to protect the identity of the research participants. Confidentiality encompasses the due regard for privacy of the research participant, and applies before, during, and after the research. In the current scenario, maintaining confidentiality has been even more important as information about individuals can become easily available through the internet, and searching for someone does not take too much time and effort. Thus, heightened caution about confidentiality issues is desired.

Before the enrolment into the study, the identity of the potential participants at a particular location is at stake as many of them would be identifiable by some of their characteristics. For example, if a study specifically mentions that the study is being conducted to understand sexual dysfunction among a handful of injecting drug users using pentazocine at location X, it may be relatively easy to find out who these individuals in location X are. Thus, efforts are required to conceal the identity of the participants as much as possible. The other issue involve ensuring confidentiality during the process of data gathering. The data or information obtained from the participant should be kept confidential to the extent possible, and be accessible to only appropriate authority apart from the researchers. For example, if the data collection and information from participants are available to the ward staff when the researcher wants to look at the inpatient setting’s satisfaction, then that information can be misused to target those who give unfavourable feedback and ratings. As data is largely kept in the digital format in the current circumstances, it may be important to safeguard the digital format of the data of participants to ensure confidentiality.

RISK MINIMIZATION AND PRECAUTIONS

Many types of research endeavours have some inherent risks. The risks that are inherent to the research design can be of various types. One of the risks of intervention studies is the adverse events associated with one or more intervention agents. For example, escitalopram can be associated with gastritis as an adverse drug reaction, or a session of repetitive transcranial magnetic stimulation can be associated with headaches. On the other hand, a participant may be exposed to worsening of the condition by remaining untreated when an inert placebo group is being used. Another risk arising from the participation in research could be or risk of injury during standard investigational procedures (like drawing blood samples for chemical estimation). Even observational studies may have such risks when investigations are built into them. An additional risk of participation is the loss of confidentiality due to misdemeanor or maladroit data handling procedures.

The researchers have the responsibility to make efforts to minimize risk to participants to the extent possible. This may include foregoing the research endeavor in the select circumstances where the considered risk may be unacceptable. In other circumstances, for example, drug trials, systems should be in place for continued monitoring of the adverse events as they occur. Sometimes, it might be difficult to ascribe an adverse event to a particular intervention. For example, after taking escitalopram, gastritis may be due to escitalopram, dietary preferences, or alcohol use or another preexisting condition. Therein, it is a standard practice to note whatever adverse event is there with some efforts to understand the causality. Additionally, many interventional studies are covered by insurance to compensate for any serious adverse events. To prevent participants receiving inactive placebo, many intervention studies use an active comparator to compare the new intervention. Such trial designs are considered as noninferiority trials. Also, research efforts aim to reduce general risks to participants by reducing the number of sample collections to bare minimum needed. The sample size requirement in the study design is kept to the bare minimum required to provide statistically accurate answers. Practices have been developed to ensure appropriate data handling. Researchers have the opportunity and moral obligation to avoid risks to their participants, and this should be carefully considered when planning the research.

ACCOUNTABILITY AND TRANSPARENCY

The researchers need to follow the principles of accountability and transparency during the entire process of conduct of the research/study. The ethical principles of accountability and transparency suggest that the researchers should make their full disclosure regarding every aspect of their interest in the research and mention their conflicts of interest truthfully.[1] The research should be conducted in all possible fair, honest and impartial manners. All the records pertinent to the research need to be retained for a reasonable time period for postresearch monitoring, evaluation of fidelity of the research findings, further research, and scrutiny by the appropriate authority, i.e., legal, regulatory or any other administrative agency, if necessary.[12425]

ETHICS OF CONDUCTING RESEARCH AND DATA HANDLING

Researches generate data, and ethical considerations of handling and processing the data is also important. One of the important aspects concerns addressing the reliability of data. The more reliable the data, the greater is likelihood of deriving scientifically accurate results. Thus, efforts to improve the data reliability are important. Apart from using sound data gathering systems, these include means to ensure the correctness and completeness of the data. Hence, while collecting the data, the researchers should try to ensure that data on all the scales and other documents is recorded completely at the time of assessment of the participants, missing data is made a note of, the data thus gathered (including the informed consent form) are stored safely and only people authorized, have access to the data. If the data are being digitally generated or kept, then access protocols should be enforced to ensure confidentiality. Digital data can be stored in a device or in the cloud and should be encrypted when possible to enhance confidentiality.

ETHICAL ISSUES RELATED TO DATA MANAGEMENT, DATA PRESERVATION AND SHARING

In addition to informed consent and data collection, the ethical principles of research also apply to data management, data preservation and sharing.

Data management

The principal investigator or the researcher is the primary person who is solely responsible for management, preservation (including security and storage), and retention of all the data related to the research project. The researchers also have the responsibility of informing the study participants about their obligations in relation to information collected from them. It is ideal to provide information to the participants in the informed consent about the possible use of the data collected in the future and assurance of data sharing with anonymity maintained. The researchers should lay down their policy for who will access to the research data. They should provide rights to access to personal data only among the research group members. Anonymisation of data should be done, i.e. the data’s identifiers should be changed to maintain data privacy (such as by removing, substituted, distorting identifying variables, etc.). A person’s identity can be easily known from the direct identifiers (e.g., names, addresses, E-mail address, telephone number, etc.) or from the indirect identifiers (e.g., information about workplace, occupation characteristics, and age, etc.). Some of the data anonymization techniques include removing major identifying data, removing all identifying data, replacing with descriptions (for example, codes) that reflect the significance of the identification, and using aggregate categories to reduce precision (such as income category, age group category, etc.). Further, all the changes made in the data should be documented.

Data preservation

Proper provisions for the storage of data reflect the sensitivity of the data collection. One of the important responsibilities of the principal investigator’s and other researchers is to have appropriate levels of storage security with stringent policies for the unauthorized access to data, stored either in physical and electronic forms. Additionally, appropriate measures must be in place for the retention of data for appropriate periods following the end of the project, which can vary depending on the nature of the research and the type of data collected. This is usually determined from project to project, but the data may be kept till 5 years after completion of the study. However, for the sponsored studies or intervention trials, the retention period is usually governed by the retention periods and conditions imposed by research sponsors in the drug trial agreement records. After the retention period, the data must be securely deleted or destroyed as applicable to the nature of data involved.

Data sharing

The Principal Investigator and/or researchers have the responsibility of making the data available to others for future use. For this purpose, the data can be shared with other researchers or third parties with proper maintenance of ethical principles. The personal data in any form should not be shared with a third party unless specific and explicit consent has been obtained during data collection process. Sharing of anonymized data with a third party, must be covered by valid consent of the participant. The researchers need to think critically about how the research data can be shared, under what limitations and prohibitions and seek guidance from IRB when needed.

MAKING RESEARCH AVAILABLE TO OTHERS

Research data can be made available to others for several research purposes such as on request by other researchers in relation to any ongoing study similar to the research done or to be included in any meta-analysis/systematic reviews etc. However, certain ethical principles need to be kept in mind in this regard. Some of these are:

Data pertaining to sensitive personal details need to be avoided from sharing unless proper consent has been taken and the data has been de-identified adequately.

Some part of the data can be published or a brief description of data can be made available to others so that researchers in the same field can cite it.

The data can be made open accessible to all by following open access publication strategies of some journals.

Certain conditions can be placed for accessibility of data (such as mailing to the corresponding author mentioning reasons for use of data, etc).

ANALYSIS OF DATA

When coding and analysis of the data, if people outside the research team are involved, it is important to hand over only the de-identified data to ensure that confidentiality of the study participants is maintained. It is also important that the analysis plan should be predecided at the time of designing the research and the researchers need to follow the same. Similarly, while transferring data to other colleagues, it is preferable to share anonymized data which removes the identifying information. Hard-copies of the data should also be suitably stored to ensure confidentiality, and final disposing of the hard copies should be done with due diligence, and shredding may be used.

ISSUES RELATED TO INTERIM ANALYSIS OF THE RESEARCH/STUDY

The continual stream of data should also be subjected to interim analysis, especially in clinical trials. The interim analysis helps to ascertain the whether the primary objectives have been met. If so, the trial can be stopped so that other potential participants are not subjected to the risk of harm due to participation. Also, continued evaluation of risks is important, and after considerations for serious adverse events reported in the study, the intervention trial can be stopped is harms are deemed unacceptable. Such serious adverse events should be reported to the ethics committees, and they might be able to make a more unbiased decision for trial termination if the risks are high.

Interim analysis is one of the reliable rational approaches to clinical trials that incorporate the information which is learned during the course of a clinical study and how it is completed, without compromising the validity or integrity. This method and interim results may lead to changes in the logistics, monitoring, and recruitment procedures to an ongoing trial. The simplest result of such an interim analysis is early stoppage of the study. This approach is regarded as rational as it allows the researchers to devise management plans utilizing the real-time data and to take prompt decisions.[26] In this regard, it is essential to note that while the investigators should remain blinded till the end point of the study, the data safety monitoring board of the trial can be partially or fully unblinded at the time of first interim analysis and there should not be any bias at this time so as to preserve the quality and authenticity of the study. However, it is important to note that the study design, once approved by the IRB/IEC, should not be changed based on the interim results unless there is a suspicion on the accuracy or the estimated risks to the study subjects high.

Publication of interim results of randomized trials is at times questioned ethically. It is said that this can at times undermine the trial integrity by unblinding or encourage dropouts and crossovers, which can result in uncertainty about the findings because results based on fewer outcomes are less precise and/or can lead to overstating true treatment effects.[2728] Systematic reviews of published interim results of randomized controlled trials in peer-reviewed journals suggest that publication of interim results of trials are often associated with larger treatment effects, compared to the treatment effects reported for the final completed trial.[29]

With regard to interim testing strategies in psychiatric research, a thorough a-priori planning and specification before the study commences need to be planned as in many cases it has been that to exploratory hunting or fishing for significance at some unplanned interim stages is likely to cause Type I error inflation because of uncontrolled multiple testing which can be lead to overestimation or underestimation of study findings.[30]

ISSUES RELATED TO TERMINATION OF STUDIES, PRIOR TO COMPLETION

It has been often seen that clinical trial investigators strive to reduce the number of participants in their studies and arrive at a rapid decision about treatment effects for various reasons (e.g., lower study costs). However, two important rules need to be kept in mind in relation to termination of studies prior to completion.[3132] The first rule suggests possible stoppage for the benefit if the early interim analysis data provides reasonable evidence of an important treatment effect, in favour of the experimental drug arm, after controlling for all potential statistical corrections. Second rule for termination of a study concerns due to possible fatality or serious adverse side effects found during the interim data analysis. Therefore, the study’s continuation is unlikely to provide any potential benefit. Further, the investigators can also call off the study if an interim analysis found very minimal difference between the control and experimental arms or if the control treatment is found to be superior. In such scenarios, calculation of conditional power (i.e., the chances of obtaining a statistically significant result if the study is allowed to proceed) needs to be done and all these data have to be provided to the IRB for proper maintenance of records.

MHCA, 2017 AND PSYCHIATRY RESEARCH

The MHCA, 2017 has recognized the importance of research in the field of psychiatry.[16] The section 99 of MHCA, 2017 focuses on mental health research. The framework of research in the MHCA seems to be in line with globally accepted principles. However, there are some procedural issues that would need clarification and streamlining later. For example, the process of application, deliberation and approval from State Mental Health Authority for research; procedures for dealing with irregularities and infringements; and manner of elicitation and confirmation of “free” and “informed” consent from the participants.

The section 99 of MHCA clearly spells out the scope and procedural elements in research conducted among individuals with mental illnesses. The Act mentions that any research involving interviewing the person or involving carrying out any psychological, physical, chemical or medicinal interventions needs to have “free”, and informed consent from the individuals with mental illnesses. So, the Act caters to interventional studies and addresses the issues relevant to the observational studies that gather information through an interview. The responsibility to get the consent rests upon the professionals conducting the research. The logical extension is the individual or group of individuals conducting the research should be professionals from some profession and not lay individuals.

The section also mentions that if a study aims to conduct an intervention among individuals with mental illness who are unable to provide free and informed consent but do not resist participation in such a study, such research shall be carried out after obtaining permission from concerned State Authority. In such situations, the State Authority has the power to allow such research with informed consent being obtained from nominated representative if the Authority is satisfied that the proposed research cannot be performed on persons who are capable of giving free and informed consent; and the proposed research is necessary to promote the mental health of the population, to which the prospective research participant belongs to; and the proposed research is designed to gain knowledge relevant to the particular mental health needs of persons with mental illness. In such a situation, the persons and organizations conducting the proposed research are required to make full disclosure of the interests with no conflict of interest being involved; and the proposed research need to be approved by the ethical committee of the institute and the conduct of the research should adhere to the national and international guidelines and regulations. This has been done to safeguard the rights of the individuals among whom the research would be conducted. People with mental illnesses who are unable to provide informed consent themselves are likely to be disenfranchised and vulnerable, and hence extra care has been prescribed to safeguard their rights.

The same section of MHCA also mentions that research based upon notes of a person who is unable to provide free and informed consent would not be restricted. The caveat in this situation being the anonymity of the individual should be maintained.

The Act also clarifies that if the person with mental illness has given consent or the consistent is provided by the nominated representative, they can withdraw the consent any time during the research period. This is in line with current conventions that dictate allowing the participants to withdraw from participation without loss of benefits they are otherwise entitled to.

ISSUES RELATED TO ONLINE/WEB-BASED SURVEYS

In recent times, many research projects are being carried out partly or completely by using online means and this has become more popular during the COVID-19 pandemic. The issues which are pertinent to the online-survey’s include recruitment and consent, protection of confidentiality and privacy of the participants’ identity and/or responses, criticisms related to multiple responses by one individual, issues related to snowball sampling technique, and generalization of the study results.[33]

With regard to web-based/email surveys, it is suggested that the the consent form should be in the similar format as it is for conventional research, except that there should be an option/button to click ‘I accept’ with a statement. Clicking this button implies that the person provides his consent to participate in the study, and the survey program will proceed with the study presentation only after this. Electronic signatures in such cases are not required. If the recruitment is done through the web/email, the participant can also either E-mail back the consent form or make a response directly via the web page, which can be recorded for the investigator. However, the criticisms of such consent is that it is not possible to verify if the participant had gone through the details of the information sheet and the consent form carefully, have understood properly and whether they have been able to comprehend the information provided or whether the person who is giving the consent to participate actually participates, i.e. issues related to authenticity of the subject participation.[34] Moreover, information related to certain particulars like age or mental capacity to give consent cannot be ascertained.[35]

With regard to the confidentiality and anonymity of online surveys, some of the researchers use third-party software to carry out the online surveys and other forms of data collection. While carrying out online surveys, especially those involving collection of sensitive information from the participants, the research protocol should be explicit about what software system or vendor is being used to implement the study (e.g. Survey Monkey/Google Forms, etc.), and the researchers need to explain about the system’s privacy protections. It can be mentioned in the protocol as to whether the IP addresses of respondents will be collected, and if collected, how these will be handled. Anonymity can be ensured by stating that no questions will be asked for identifying information, such as E-mail address, phone number, and name.

In this regard, a report of the Advisory Panel on Public Opinion Survey Quality from Canada[36] and Social Sciences and Humanities Research Ethics Special Working Committee (SSHWC, 2008)[37] have provided certain code of conduct and have enlisted various steps to be taken to ensure ethical practice while performing online surveys [Table 8].

Table 8

Ethical issues involved in online surveys

• Participation must be voluntary

• Avoid misleading statements, provide information to the potential participants to make them well aware about the type, nature and the purpose of the research for which their data will be collected and used

• Avoid collecting personal information without the prior knowledge of the participants and anonymity of data is maintained

• Provide information to the potential participants about the language in which the survey is available

• Personally identifiable data, if collected, should be kept and stored separately

• Personal information should not be used for subsequent nonresearch purposes

• Provide information to the potential respondents about the duration of the survey, information about data protection, privacy policy, cookie policy statements

The online survey studies also have to go through the same process of ethical approval by local/IEC before the start of the survey. The protocol should explicitly mention all details of the survey procedure, including ethical issues and survey software.

ETHICAL ISSUES RELATED TO RETROSPECTIVE STUDIES

Retrospective studies are conducted on the already available data or stored biological samples collected at some point of time from the study subjects. The study subjects are not necessarily aware that their data or samples are being used for a purpose other than their own treatment. In this regard, there can be two situations i.e., (1) The clinicians analyze the data collected as part of the routine clinical care from the patients’ treatment records and (2) the researcher analyze the data available with the third parties within the hospital.[38]

In the former scenario of retrospective data analysis, the cardinal rule of law on data protection (LPD) needs to be followed, which states that the data can only be used only for the purpose which was initially indicated or implied to the person who provided the data. For proper ethical reasons, contacting the patients and obtaining their consent if they wish to allow the researcher to analyse the data for some other research purpose need to be considered. However, there can be some exceptions to this LPD rule too. If the patient data is used for research purposes, provided that the results are published which does not reveal the patient’s identification, patient consent may not be required. However, the researchers need to go through the ethical approval process by the IRB and the protocol must state how the expected benefits from the proposed research pose no potential risks/harms to the subjects.[38] The later situation (third party participation) is not ethical with regard to psychiatric retrospective research. Hence, data sharing to third parties unless approved by the IRB with justifiable reasons is usually not permitted.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.